Dental plaque and other biofilms in the oral cavity play an important role in the etiology of dental caries, gingivitis and periodontitis. The pathogenic potential of the organisms comprising the multi-species ecosytems is multi-faceted. However, it is clear that the end products of amino and sugar fermentations by oral microorganisms, are contributing factors in the development of these and other diseases. The metabolic products formed by Gram-positive streptococci (eg. Streptococcus mutans) and Gram-negative anaerobic species (eg. Fusobacterium nucleatum ) include short-chain carboxylic acids and sulfur-containing derivatives. The demineralizing action of organic acids upon the tooth surface has long been recognized, and the potent cytotoxicity of sulfides and mercaptans toward epithelial cells has also been documented. Surprisingly, little is known concerning the regulation of the genes and enzymes that constitute these different fermentation pathways in oral bacteria. Furthermore, although Fusobacteria- including F. nucleatum - contain a variety of sulfhydrase and desulfhydrases, these enzymes have yet to be characterized at the genetic, structural and catalytic levels. The goals of this program are two-fold. First, to purify and characterize the enzymes that constitute the energy-yielding pathways of oral bacteria. Second, to elucidate the genetic and biochemical mechanisms responsible for the regulation of expression and catalytic activity of these proteins.